title: Calcium supplementation prevents endothelial cell activation: possible relevance to preeclampsia.
abstract: OBJECTIVE
  Preeclampsia is a leading cause of maternal and fetal mortality and morbidity. A hallmark of preeclampsia is endothelial cell dysfunction/activation in response to 'toxins' from the placenta. Necrotic trophoblastic debris (NTD) is one possible placental toxin and other activators of endothelial cells include inflammatory cytokines. Calcium supplementation appears to protect 'at-risk' women from developing preeclampsia but how is unclear.
  
  
  METHODS
  Placental explants were cultured with interleukin-6 (IL-6) in varied concentrations of calcium. The resultant trophoblastic debris was exposed to endothelial cells. Endothelial cells were exposed to activators including NTD, IL-6, and preeclamptic sera in the presence of varied concentrations of calcium and activation monitored by quantifying cell surface markers by ELISA.
  
  
  RESULTS
  Raising the levels of calcium did not prevent the IL-6-induced shedding of NTD from placental explants but did prevent the activation of endothelial cells in response to IL-6, preeclamptic sera, or NTD. Reducing the level of calcium directly induced the activation of endothelial cells. Inhibiting nitric oxide synthetase ablated the ability of high calcium levels to protect endothelial cell activation. The activity of endothelial cell nitric oxide synthetase was blocked with L-N-nitroarginine methyl ester.
  
  
  CONCLUSIONS
  Our results demonstrate calcium levels do not affect the shedding of trophoblastic debris but are important to endothelial cell activation and supplemental calcium may reverse the activation of the endothelium in preeclamptic women. These results may in part explain the benefits of calcium supplementation in the reduction of risk for developing preeclampsia and provide in-vitro mechanistic support for the use of calcium supplementation in at-risk women.
authors.affiliation: aDepartment of Obstetrics & Gynaecology, The University of Auckland, Auckland, New Zealand bWuxi Maternity and Child Health Hospital Affiliated Nanjing Medical University, Wuxi, China cMaternal Fetal Medicine, Auckland City Hospital dGravida The National Centre for Growth and Development, The University of Auckland, Auckland, New Zealand.
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Mancy
authors.initials: M
authors.lastname: Tong
authors.forename: Man
authors.initials: M
authors.lastname: Wu
authors.forename: Peter R
authors.initials: PR
authors.lastname: Stone
authors.forename: Saul
authors.initials: S
authors.lastname: Snowise
authors.forename: Lawrence W
authors.initials: LW
authors.lastname: Chamley
mesh_terms: D002118:Calcium / Q000008:administration & dosage* / Q000378:metabolism*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D049109:Cell Proliferation; D002470:Cell Survival; D003470:Culture Media; D019587:Dietary Supplements; D042783:Endothelial Cells / Q000166:cytology / Q000187:drug effects*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007249:Inflammation; D015850:Interleukin-6 / Q000494:pharmacology; D008833:Microcirculation; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009336:Necrosis; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D010920:Placenta / Q000378:metabolism; D011225:Pre-Eclampsia / Q000378:metabolism* / Q000473:pathology*; D011247:Pregnancy; D014327:Trophoblasts / Q000378:metabolism
chemical_list: D003470:Culture Media; D015850:Interleukin-6; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D002118:Calcium; D019331:NG-Nitroarginine Methyl Ester